PMID- 33602684
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20220316
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 27
IP  - 10
DP  - 2021 May 15
TI  - Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the 
      INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22.
PG  - 2742-2754
LID - 10.1158/1078-0432.CCR-20-2399 [doi]
AB  - PURPOSE: We assessed the relationship between cluster of differentiation-22 
      (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care 
      (SC) in INO-VATE (NCT01564784). PATIENTS AND METHODS: Adults with 
      relapsed/refractory B-cell precursor CD22-positive (by local or central 
      laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin 
      (n = 164) or SC (n = 162). Outcomes were analyzed by baseline CD22 positivity 
      (percentage of leukemic blasts CD22 positive, >/=90% vs. <90%) and CD22 receptor 
      density [molecules of equivalent soluble fluorochrome (MESF), quartile analysis]. 
      RESULTS: Most patients had high (>/=90%) CD22 positivity per central laboratory. 
      The response rate was significantly higher with inotuzumab ozogamicin versus SC. 
      Minimal/measurable residual disease negativity, duration of remission (DoR), 
      progression-free survival, and overall survival (OS) were significantly better 
      with inotuzumab ozogamicin versus SC in patients with CD22 positivity >/=90%. Fewer 
      patients had CD22 positivity <90%; for whom, response rates were higher with 
      inotuzumab ozogamicin versus SC, but DoR and OS appeared similar. Similar trends 
      were evident in quartile analyses of CD22 MESF and CD22 positivity per local 
      laboratory. Among inotuzumab ozogamicin-responding patients with subsequent 
      relapse, decrease in CD22 positivity and receptor density was evident, but not 
      the emergence of CD22 negativity. Rates of grade >/=3 hematologic adverse events 
      (AEs) were similar and hepatobiliary AEs rate was higher for inotuzumab 
      ozogamicin versus SC. No apparent relationship was observed between the rates of 
      hematologic and hepatic AEs and CD22 expression. CONCLUSIONS: Inotuzumab 
      ozogamicin demonstrated a favorable benefit-risk profile versus SC in patients 
      with higher and lower CD22 expression. Patients with high CD22 expression and 
      normal cytogenetics benefited the most from inotuzumab ozogamicin therapy.
CI  - (c)2021 American Association for Cancer Research.
FAU - Kantarjian, Hagop M
AU  - Kantarjian HM
AD  - MD Anderson Cancer Center, University of Texas, Houston, Texas. 
      hkantarjian@mdanderson.org.
FAU - Stock, Wendy
AU  - Stock W
AD  - University of Chicago, Chicago, Illinois.
FAU - Cassaday, Ryan D
AU  - Cassaday RD
AUID- ORCID: 0000-0002-3424-2425
AD  - University of Washington School of Medicine and Fred Hutchinson Cancer Research 
      Center, Seattle, Washington.
FAU - DeAngelo, Daniel J
AU  - DeAngelo DJ
AUID- ORCID: 0000-0001-7865-2306
AD  - Dana-Farber Cancer Institute, Boston, Massachusetts.
FAU - Jabbour, Elias
AU  - Jabbour E
AD  - MD Anderson Cancer Center, University of Texas, Houston, Texas.
FAU - O'Brien, Susan M
AU  - O'Brien SM
AD  - Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, 
      California.
FAU - Stelljes, Matthias
AU  - Stelljes M
AD  - Universitatsklinikum Munster, Munster, Germany.
FAU - Wang, Tao
AU  - Wang T
AD  - Pfizer Inc., Cambridge, Massachusetts.
FAU - Paccagnella, M Luisa
AU  - Paccagnella ML
AD  - Pfizer Inc., Groton, Connecticut.
FAU - Nguyen, Kevin
AU  - Nguyen K
AD  - Navigate BioPharma Services, Inc., a Novartis subsidiary, Carlsbad, California.
FAU - Sleight, Barbara
AU  - Sleight B
AD  - Pfizer Inc., Groton, Connecticut.
FAU - Vandendries, Erik
AU  - Vandendries E
AD  - Pfizer Inc., Cambridge, Massachusetts.
FAU - Neuhof, Alexander
AU  - Neuhof A
AD  - Pfizer Pharma GmbH, Berlin, Germany.
FAU - Laird, A Douglas
AU  - Laird AD
AD  - Pfizer Inc., San Francisco, California.
FAU - Advani, Anjali S
AU  - Advani AS
AD  - Cleveland Clinic, Cleveland, Ohio.
LA  - eng
SI  - ClinicalTrials.gov/NCT01564784
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210218
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (CD22 protein, human)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 2)
RN  - P93RUU11P7 (Inotuzumab Ozogamicin)
SB  - IM
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Disease Management
MH  - Disease Susceptibility
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Inotuzumab Ozogamicin/administration & dosage/adverse effects/*therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug 
      therapy/etiology/metabolism/*pathology
MH  - Recurrence
MH  - Retreatment
MH  - Sialic Acid Binding Ig-like Lectin 2/metabolism
MH  - Treatment Outcome
EDAT- 2021/02/20 06:00
MHDA- 2022/03/17 06:00
CRDT- 2021/02/19 05:54
PHST- 2020/06/21 00:00 [received]
PHST- 2020/12/03 00:00 [revised]
PHST- 2021/02/10 00:00 [accepted]
PHST- 2021/02/20 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/02/19 05:54 [entrez]
AID - 1078-0432.CCR-20-2399 [pii]
AID - 10.1158/1078-0432.CCR-20-2399 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2021 May 15;27(10):2742-2754. doi: 
      10.1158/1078-0432.CCR-20-2399. Epub 2021 Feb 18.